Chloroquine Inhibits Ca2+ Signaling in Murine CD4+ Thymocytes

التفاصيل البيبلوغرافية
العنوان: Chloroquine Inhibits Ca2+ Signaling in Murine CD4+ Thymocytes
المؤلفون: Qing-Hua Liu, Guangju Ji, Jinhua Shen, Jin-Chao Xu, Yong Bo Peng, Gangjian Qin, Yi Fan Wu, Ming Yu Wei, Donglin Guo
المصدر: Cellular Physiology and Biochemistry, Vol 36, Iss 1, Pp 133-140 (2015)
بيانات النشر: Cell Physiol Biochem Press GmbH & Co KG, 2015.
سنة النشر: 2015
مصطلحات موضوعية: CD4-Positive T-Lymphocytes, Male, Thapsigargin, Physiology, T cell, IP3 receptor, Biology, Pharmacology, Transient receptor potential C3 (TRPC3), lcsh:Physiology, lcsh:Biochemistry, chemistry.chemical_compound, Mice, TRPC3, Chloroquine, Caffeine, medicine, Extracellular, Animals, lcsh:QD415-436, Calcium Signaling, Cells, Cultured, Thymocytes, lcsh:QP1-981, Inositol trisphosphate receptor, Molecular biology, CD4+ T cells, EGTA, medicine.anatomical_structure, chemistry, Gene Expression Regulation, Pyrazoles, Calcium, Intracellular, medicine.drug
الوصف: Background/Aims: Bitter-tasting chloroquine can suppress T cell activation by inhibiting Ca2+ signaling. However, the mechanism of inhibition remains largely unclear. Methods: In this study, CD4+ T cells were isolated from the thymus, and the calcium content of CD4+ thymocytes was measured using fura-2 AM and a TILL imaging system. Pyrazole-3 (Pyr3), thapsigargin (TG), and caffeine were used to assess the effects of chloroquine on the intracellular Ca2+ content of CD4+ T cells. Results: In murine CD4+ thymocytes, chloroquine decreased the TG-triggered intracellular Ca2+ increase in a dose-dependent manner. In the absence of chloroquine under Ca2+-free conditions (0 mM Ca2+ and 0.5 mM EGTA), TG induced a transient Ca2+ increase. After restoration of the extracellular Ca2+ concentration to 2 mM, a dramatic Ca2+ increase occurred. This elevation was completely blocked by chloroquine and was markedly inhibited by Pyr3, a selective antagonist of transient receptor potential C3 (TRPC3) channel and stromal interaction molecule (STIM)/Orai channel. Furthermore, the TG-induced transient Ca2+ increase under Ca2+-free conditions was eliminated in the presence of chloroquine. Chloroquine also blocked the dialyzed inositol-1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ increase. However, chloroquine was not able to decrease the caffeine-induced Ca2+ increase. Conclusion: These data indicate that chloroquine inhibits the elevation of intracellular Ca2+ in thymic CD4+ T cells by inhibiting IP3 receptor-mediated Ca2+ release from intracellular stores and TRPC3 channel-mediated and/or STIM/Orai channel-mediated Ca2+ influx.
اللغة: English
تدمد: 1421-9778
1015-8987
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::266b6ff533044ffe1ea15d13250a5aae
http://www.karger.com/Article/FullText/374058
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....266b6ff533044ffe1ea15d13250a5aae
قاعدة البيانات: OpenAIRE